Drug treats depression in hours

A drug known on the street as “Special K” could be the newest innovation in anti-depression treatment.

In a review article published in “Science” on Oct. 5, Ronald Duman and George Aghajanian, psychiatry professors at the Yale School of Medicine, brought together more than a decade of research on the drug ketamine and its potential to become the first new class of anti-depressant medication in over 50 years. Though ketamine causes psychosis in high doses, scientists have found that low doses can reverse the signs of depression — and even suicidal urges — in just a few hours.

“The idea that a drug could produce a rapid improvement rather than taking several months to feel better is really an important idea and it really challenges the thinking about how anti-depressant medications might work,” Yale Chair of Psychiatry John Krystal said. “I think [it provides] a lot of hope for the future for the treatment of depression.”

Krystal, along with his collaborator Dennis Charney, was the first to link ketamine to the alleviation of depression in the 1990s. Ketamine has long been used as a pediatric and veterinary anesthetic and was originally explored by psychiatrists as a way to study schizophrenia, Krystal said.

Traditional anti-depressants, known as SSRIs, have been shown to take an average of seven weeks to produce improvement in major depressive disorder, Krystal said. Patients must take medication daily, and for one third of these patients, current medications provide no relief, he added. By contrast, ketamine rapidly reverses the disease’s physiological and behavioral effects. Ketamine has been shown to alleviate symptoms of depression in 70 percent of those patients who previously did not respond to treatment, Duman said.

Duman’s work has contributed to the understanding of the pathway by which ketamine works. While SSRIs block the re-uptake of serotonin, a neurotransmitter commonly thought to contribute to feelings of well-being, ketamine acts on the glutamate neurotransmitter system, which mediates the fast transfer of information in the brain.

“We think that’s why ketamine is able to produce such a rapid response,” Duman said.

While chronic stress and depression lead to the loss of synapses ­— key connections between cells that play a critical role in all brain function, including mood and emotion — ketamine reverses this degenerative process. The drug both stimulates synaptic growth and removes inhibitions to regeneration.

“Ketamine effectively takes your foot off the break and steps on the gas,” Krystal said.

The review’s findings are “totally against what we’ve always believed about degenerative disorders,” said Aghajanian, the paper’s coauthor.

“Depression is a neurodegenerative disease, and people long thought that it was very hard to reverse such a thing,” Aghajanian said. “That’s the amazing thing about ketamine — it reverses the changes within 24 hours.”

Ketamine is already FDA-approved as an anesthetic, which has led some doctors to begin prescribing it “off-label” to severely depressed or suicidal patients. This practice is concerning, Krystal said, because the drug is still in the experimental stages and has considerable risks, from potential abuse to side effects that may resemble schizophrenia. In addition, patients relapse after one to two weeks, losing the new synapses formed and the corresponding improvement in their depression. Research into the safety of re-administering the drug is still ongoing.

Aghajanian said researchers are now looking for safer alternatives to ketamine. These alternatives — several of which are currently in clinical trials — would hopefully follow the same pathway as ketamine but cause fewer side effects, he added. Another area for further development is the drug’s method of administration. Ketamine is currently administered intravenously, but future research will explore ways to deliver the drug orally or intra-nasally.

“All this work has really stimulated a back and forth between bench and bedside research around the world,” said Carlos Zarate, a researcher in the Mood and Anxiety Disorders Program at the National Institute of Mental Health (NIMH). “So that’s the exciting part — it’s actually luring industry back into psychiatry, at least on the depression side.”

Each year, major depressive disorder affects 14.8 million Americans over the age of 18 — 6.7 percent of the U.S. population, according to the NIMH.

Comments

gdavis144

I love statistics! Curent meds don’t work for “1/3″ but ketamine doesn’t work for only 30%. Sounds like a billion dollar industry.

bk15

I love fractions! Ketamine doesn’t work for 30% of the third for whom SSRI doesn’t work. Sounds like reading closely would be a great idea.

The Anti-Yale

Has anyone ever thought of trying to tackle the problem which causes depression—-the emptiness of materialism?

We all know materialism has become our false idol, and yet we continue our hosannahs.

amenhotep

Depression is a neurodegenerative disease. It has been around forever, and it exists in non-human animals. The only reason we “have” more of it today is that we recognize it as a disease and diagnose it.

Quals

Ugh, I really don’t like having to agree with PK, but yeah, he is right. While some psychiatric disorders are clearly genetic in origin and are 100% diseases, plain vanilla depression is mostly due to folks lacking a coherent philosophy of life and pursuing hedonistic materialism.

Most theories suggest that depression has both biological and psycho/social components.

penny_lane

I know it’s not intended this way, but statements like these are just plain offensive to people like me who actually have depression. Get off your high horse, have a little respect, and think before you speak please.

rbg1943

Please, Yale, it’s still important.”…takes your foot off the break (SB ‘brake’) and steps on the gas.”

“The only reason we “have” more of it today is that we recognize it as a disease and diagnose it.”

Nonsense.

The emptiness of materialism expands depression in exact proportion to our unacknowledged worship of materialism.

whatwhat

so please explain why research on heredity of depression within families shows that if you have a parent or sibling that has had major depression, you may be 1.5 to 3 times more likely to develop the condition than those who do not have a close relative with the condition?

The Anti-Yale

People used to deal with depression through religion, through parenting, through,

The Anti-Yale

[to continue]
encouraging resilience. (I’m NOT talking about severe depression, I’m talking about the “normal” depression which used to be considered a part of life and now is considered something to be “treated”.)

It is the “mixed strand” of emotions which enriches life. A single frequency joy-stick approach to life is unbalanced and phony.

Depression is often an appropriate response, not an illness.

BubbaJoe123

People also used to treat cavities by just pulling teeth, and gunshot wounds with amputation. The fact that the physical signs of depression are less clear makes it no less a real medical condition. Your position amounts to an approach of “walk it off.”

penny_lane

What seems important to me is the distinction between the clinical term depression, and our words for emotions (sadness, grief, ennui) that are unpleasant but necessary parts of life. Depression does have mood components (sadness and/or anhedonia), but it’s also so much more (sleep disturbance, difficulty with motor skills, changes in appetite). Bereavement used to preclude a diagnosis of depression, but they’re changing the criteria so that people who experience the latter symptoms after a loss can get help. For better or for worse? I guess we’ll see.

The distinction between the normal and the abnormal is a really important philosophical question, but I for one would rather err on the side of wanting to help. Take Emma Bovary as an example–perhaps she was a victim of her own fatuous materialism, but what if she had received treatment? Maybe she wouldn’t have neglected her children or committed suicide. The anti-suicide camp is a fine one by me.

Either way, I think chalking mental illness up to negative attitudes on the part of those suffering is an old stigma, one that hits people who are genuinely trying to live healthy, fulfilling lives really, really hard. I would much rather avoid sweeping generalizations, because each case of depression is as unique as the individual.